Terpene flavorant intermediates

ABSTRACT

A process for preparing compounds of the type of sinensal, which is suitable as a flavor-imparting agent of orange aroma, and novel intermediates including those having the general formula: ##SPC1## 
     Wherein R signifies a CH 2  OH, CHO or COOH group and the broken lines present a double bond emanating from C-atom 4, are disclosed.

This is a division of application Ser. No. 436,756, filed Jan. 25, 1974,which in turn is a division of application Ser. No. 742,178, filed July3, 1968, now U.S. Pat. No. 3,872,172.

SUMMARY OF THE INVENTION

This invention provides a commercially-feasible process for makingunlimited quantities of compounds of the type of the previously-raresinensal, thereby permitting the widespread use of this product as aflavorant to impart an orange flavor and aroma to food products such asorange drinks.

Novel intermediates, some of which also possess flavorant properties,are also the subject of this invention.

DETAILED DESCRIPTION OF THE INVENTION

The process in accordance with this invention for the manufacture ofcompounds of formula I is characterized in that a compound of theformula ##SPC2##

Is ozonized and the ozonization product which is obtained is decomposedto give a compound of general formula I.

Cis or trans ocimene or, preferably, myrcene can be used as the startingmaterial of formula II.

If in formulae I and II the double bond which is conjugated with theterminal double bond lies within the chain (as is the case in ocimene),formulae I and II are meant to represent not only the cis but also thetrans isomers.

The ozonization of the trienes II surprisingly proceeds with highselectivity, since the ozonide linkage is practically exclusivelyeffected at the isolated double bond, and so the conjugated double bondspractically do not enter into reaction with the ozone.

The ozonization can be undertaken according to methods known per se, bybringing ozone-containing gas into contact with the triene which is tobe ozonized, conveniently by introduction of the gas into a preferablydilute solution of the triene. Presently preferred solvents are thosewhich are inert to ozone, or at least display greater stability than thesubstance which is to be ozonized; for example, alkanes such as hexane,petroleum ether, cyclohexane; benzene and its derivatives; halogenatedhydrocarbons such as carbon tetrachloride, chloroform, methylenechloride, methyl chloride, ethyl chloride, ethyl bromide; esters such asformic acid or acetic acid esters (ethyl acetate); ketones such asacetone or methyl ethyl ketone; ethers such as dimethyl ether, diethylether, tetrahydrofuran; acid anhydrides such as acetic anhydride; acidamides such as formamide, dimethylformamide; nitromethane etc. Amongother solvents which may be used are those which enter into reactionwith the ozonide which is primarily formed: for example, carboxylicacids (for example, formic acid, acetic acid, propionic acid); alcoholssuch as methanol, ethanol, propanol; water in admixture with acetone.Best suited are solvents which are able to hold the ozonization productsin solution. Furthermore, low-boiling solvents are to be preferred,since these are usually readily separable from the reaction products.For the ozonization of myrcene and ocimene, particularly suitablesolvents are, for example: methyl chloride, chloroform, carbontetrachloride, benzene, acetone, ethyl acetate, methanol.

The concentration of the solution which is to be ozonized can varywithin wide limits. In general, dilute solutions give better yields. Onpractical grounds, 5-20% solutions will usually be used.

Conveniently, not more than about 1 mol equivalent of ozone is allowedto act on the triene II, in order to avoid an oxidation of the reactionproducts. Normally, an oxygen stream with an ozone content of about2-10% is used. However, more dilute and more concentrated ozone mixturesalso may be employed. If desired, oxygen-free ozone (as the gas or as asolution) may also be used.

The ozonization is advantageously carried out at temperatures below roomtemperature, conveniently at temperatures below 0°C. Particularly goodyields are obtained at temperatures within the range of about -50° to-90°C.

The cleavage of the ozonization products which are primarily obtained tothe compounds of general formula I can be undertaken according tomethods which are known per se.

The alcohols of the formula ##SPC3##

may be obtained by treating the ozonization product which is formed witha powerful reducing agent, of the type known to be suitable to reduceozonides to alcohols, such as a complex metal hydride (e.g. lithiumaluminum hydride or sodium borohydride), hydrogen, catalyticallyactivated by noble-or transition metals (e.g. palladium, platinum) orcomplexes of such metals (as for exampletris-triphenylphosphine-rhodiumchloride).

The aldehydes of the formula ##SPC4##

can be obtained from the ozonization products by treatment with a mildreducing agent (of the type known to be suitable to reduce ozonides toaldehydes); for example, an iodide (e.g. sodium or potassium iodide),sulphite, bisulphite (e.g. sodium bisulphite), with formaldehyde,sulphur dioxide, pyridine, hydrazine hydrate, a sulphide (e.g. dimethylsulphide), hydroquinone, zinc or magnesium in acidic solution,Raney-nickel, phosphorus (III)-compounds (.e.g. phosphines such astriphenylphosphine, tri-loweralkyl-phosphites such astrimethylphosphite, hydrogen [catalytically activated by noble-ortransitionmetals or complexes thereof (examples of such systems arePt/H₂, Pd/C/H₂.)]

The carboxylic acids of the formula ##SPC5##

(i.e. 4-methylene-5-hexenoic acid or 4-methyl-3,5-hexadienoic acid) maybe obtained from the primary products of the ozonization by treatmentwith an oxidizing agent, for example, potassium permanganate, hydrogenperoxide, peracids, chromic acid, oxygen (catalyzed by manganese orsilver salts), silver oxide, peracids (e.g. perbenzoic acid, peraceticacid), etc. Using aluminum hydrides (such as, for example, lithiumaluminum hydride), the acids Ic can be reduced directly or, if desired,in the form of their esters, to the corresponding alcohols in a knownmanner. Likewise, the acids Ic may be converted via the acid chloridesinto the amides (e.g. the corresponding N-methyl anilides orN,N-dimethyl amides) which, as is known, can be transformed into thecorresponding aldehydes of formula Ib under the influence of aluminumhydrides (such as, for example, of diisobutyl aluminum hydride orlithium diethoxy aluminum hydride). The esters derived from the acids Icmay also be directly converted into the aldehydes of formula Ib at lowertemperatures.

The alcohols, aldehydes or carboxylic acids of formulae Ia, Ib or Icwhich are obtained by ozonization of the trienes II and by subsequentreductive or oxidative cleavage of the ozonization products, as well asthe triene acetals (IV-1 and IV-2) and triene aldehydes (V-1 and V-2)are new compounds which may be used as intermediate products for themanufacture of compounds with orange aroma, especially for themanufacture of the β-sinensal occurring in orange oil (Citrus sinensal)(trans β-sinensal: 2,6-dimethyl-10-methylene-2t,6t,11-dodecatrienal), ofisomers thereof (cis β-sinensal, cis and trans -α-sinesal), as well asof analogues such as, for example, the corresponding alcohols or acidesters which are likewise distinguished by particular aromas (citrusfruit flavours), on the basis of which the compounds can be used for thearomatization, for example, of drinks.

β-sinensal and its isomers (VII), as well as the corresponding alcoholand acid ester analogues, XII and XI, respectively, may be used toimpart orange flavor in drinks by incorporation therein in very smallamounts, e.g. from 1/2 to 5 parts per million. These flavorants may beused in conventional manner, for example, in the manner in which theknown flavorant, aldehyde C-10, is used.

The aldehyde Ib-1 obtainable from myrcene, or the corresponding alcoholIa-1, may be converted into cis and trans β-sinensal in accordance withthe following schemes: ##SPC6## ##SPC7## ##SPC8## ##EQU1## Scheme A:Myrcene (II-1) is converted into the aldehyde Ib-1(4-methylene-5-hexen-1-al) by ozonisation and subsequent mild reductivecleavage of the ozonisation product. The aldehyde thus obtained isreacted with a phosphorane of general formula III [wherein Ph representsa phenyl group and each R¹ signifies a lower alkyl group which can alsobe linked with each other to form a lower alkylene group (e.g.ethylene)]in a Wittig reaction to give a triene acetal of generalformula IV-1. Formula IV-1 includes the trans isomer IVa-1 and the cisisomer IVb-1.

The manufacture of the phosphorane III (as also of the phosphoranesadditionally mentioned hereinafter) and the reaction with the carbonylcomponent IB-1 can be effected according to the methods of the Wittigreaction which are known per se (see, for example, Angewandte Chemie 71(1959), 260). In doing so, one conveniently proceeds in such a way thatthe carbonyl component is added to a freshly prepared solution orsuspension of the phosphorane.

Thereupon, [if desired separation of the mixture of the cis and transisomers (e.g. by means of preparative gas chromatography)] the trieneacetal IV-1 or the isomer triene acetal IV-2 obtained from ocimene##EQU2## wherein R¹ has the same meaning as above, is hydrolysed to thecorresponding triene aldehyde of the formula ##EQU3## (including thetrans isomer Va-1 and the cis isomer Vb-1) or to the triene aldehyde offormula ##EQU4## The hydrolysis of the acetals IV-1 and IV-2 to thealdehyde V-1 and V-2 can be brought about according to the usual methodsof acetal saponification.

Finally, the triene aldehyde V-1 or V-2 is reacted, again according toWittig, to give the tetraene aldehyde of the general formula VII-1 orVII-2: ##EQU5## by reaction with a phosphorane VI. Formula VII-1includes the trans isomer VIIa-1 (natural β-sinensal) and the cis isomerVIIb-1.

Scheme B: Myrcene (II-1) is converted by ozonisation and subsequentenergetic reductive cleavage of the ozonisation product into the alcoholIa-1 (4-methylene-5-hexen-1-ol). After transformation into thephosphorane VIII-1, this is reacted with the ketone acetal IX in aWittig reaction to give the triene acetal IV-1 which, as shown in schemeA, can then be worked up to give β-sinensal. By using ocimene asstarting material the isomeric triene acetal IV-2 can be obtainedsimilarly.

The transformation of the alcohol Ia-1 into the phosphorane VIII-1 can,for example, be undertaken in such a way that the alcoholic hydroxylgroup is exchanged for an iodine atom and the6-iodo-3-methylene-1-hexene obtained is reacted with triphenyl-phosphineto give the corresponding phosphonium iodide which, after treatment witha strong base such as butyllithium, can then proceed to the reactionwith the ketone acetal IX.

Scheme C: The phosphorane VIII-1 which is obtainable in accordance withscheme B is reacted according to Wittig with the ketone ester of generalformula X (wherein R² signifies a lower alkyl group) to give thetetraene ester XI-1, this ester is reduced to the corresponding tetraenealcohol XII-1 according to methods known per se (e.g. with lithiumaluminium hydride), and the alcohol obtained is oxidised to thecorresponding tetraene aldehyde VII-1 (β-sinensal) according to methodsknown per se (e.g. with manganese dioxide).

Scheme D: The triene aldehyde V-1 obtained according to Scheme A and Bis reacted according to Wittig with the phosphorane XIII (wherein R² isa lower alkyl group) to give the tetraene ester XI-1 and this is workedup according to Scheme C to give the tetraene aldehyde VII-1.

In an analogous manner the isomeric triene aldehyde V-2 can be convertedto the tetraene ester XI-2 ##EQU6## and this worked up via the tetraenealcohol XII-2 ##EQU7## to the tetraene aldehyde VII-2.

The following Examples illustrate the invention, all temperatures beinggiven in degrees centigrade.

EXAMPLE 1

73.5 mmol of ozone are introduced within approximately 3 hours into asolution, cooled to -80°, of 10 g (73.5 mmol) of myrcene in 50 ml ofmethanol. The still cold solution is then briefly flushed with nitrogenand treated with 6.8 g (110 mmol) of dimethyl sulphide. The cooling-bathis thereupon removed and the reaction mixture allowed to warm up. Afterapproximately 1.5 hours, the mixture is concentrated to approximatelyone-third of the volume by means of a rotary evaporator(bath-temperature maximum 30°). The residue is taken up in ether and thesolution thoroughly shaken twice with water. The solution is dried oversodium sulphate, freed from ether and the residue is distilled atwater-jet vacuum. There are obtained 6 g (74% theoretical) of4-methylene-5-hexen-1-al, boiling point 50°-55° /11 mm, IR-bands at2700, 1750, 1600, 905 cm⁻ ¹.

EXAMPLE 2

1.51 g (3.0 mmol) of finely powdered(4-ethylenedioxybutyl)-triphenyl-phosphonium iodide are suspended in 10ml of tetrahydrofuran and treated dropwise with a solution of 4.5 mmolof butyl-lithium in hexane. The solution, turns red as the phosphoniumiodide goes into solution as(4-ethylenedioxy-butylidene)-triphenyl-phosphorane. After approximately10 minutes, 0.25 ml (4.5 mmol) of methyl iodide are added to thissolution, which thereby becomes lighter, and the(4-ethylenedioxy-1-methylbutyl)-triphenyl-phosphonium iodide which isformed partially precipitates as an oil. After 10 minutes, 3.0 mmol ofbutyl-lithium in hexane are added dropwise and the solution therebyagain becomes dark red.

After 10 minutes there are added 330 mg (3.0 mmol) of4-methylene-5-hexenal (Ib-1) dissolved in 1 ml of tetrahydrofuran to thesolution containing the phosphorane III (R¹ +R¹ =ethylene). The solutionsubsequently partially decolourises and after 30 minutes, 100 mg ofsublimed potassium tertbutylate are added. The mixture is stirred for afurther 1.5 hours, then taken up in pentane and the insoluble portionwhich separates out is decanted off. The pentane extract is subsequentlywashed with water until neutral and dried over sodium sulphate. Afterremoval of the solvent, the residue is distilled. There are thusobtained 421 mg (63%) of a cis-trans isomer mixture of the triene acetalIV-1 (R¹ +R¹ =ethylene) in the form of an oil with a boiling point 160°/0.1 mm; n_(D) ²⁰ = 1.4930. IR-bands at 1600 m, 1145 s, 900 s cm⁻ ¹.

The ratio of the trans isomer IVa-1(4-methyl-8-methylene-4t,9-decadienal ethylene acetal) to the cis isomerIVb-1 (4-methyl-8-methylene-4c,9-decadienal ethylene acetal) amounts toca 1:1. The isomer mixture may be separated by means ofgas-chromatography.

The (4-ethylenedioxy-butyl)-triphenyl-phosphonium iodide (melting point172°-177°) used in this example can be obtained as follows:4-chlorobutyric acid chloride is reduced to 4-chlorobutanal according toRosenmund, the aldehyde is acetalised with ethyleneglycol, the productobtained thereby is converted with sodium iodide into the ethyleneacetal of 4-iodobutanal and the latter is reacted withtriphenyl-phosphine.

EXAMPLE 3

146 mg (0.65 mmol) of the triene ethylene acetal of formula IV-1(cis-trans isomer mixture) are dissolved in 3.7 ml of dioxan and 1.2 mlof 0.1-N sulphuric acid. The solution is boiled at reflux for 2 hours,the reaction product is taken up in ether, this solution washed untilneutral with sodium bicarbonate solution and dried over sodium sulphate.After removal of the solvent, the oily residue is distilled. There arethus obtained 97 mg (83%) of a cis-trans isomer mixture of the trienealdehyde V-1,4-methyl-8-methylene-4,9-decadienal, of boiling point 100°/0.1 mm.

In an analogous manner, the pure cis and trans isomers IVb-1 and IVa-1(obtained from the isomer mixture IV-1 by means of preparative gaschromatography) are saponified to the cis isomer Vb-1(4-methyl-8-methylene-4c,9-decadienal) and to the trans isomer Va-1(4-methyl-8-methylene-4t,9-decadienal) respectively. n_(D) ²⁰ value andIR spectrum of the two isomers obtained are identical: n_(D) ²⁰ 1.4909;IR-bands at 2700 m, 1725 s, 1600 m, 900 s cm⁻ ¹.

EXAMPLE 4

175 mg (0.98 mmol) of the trans triene aldehyde Va-1(4-methyl-8-methylene-4t,9-decadienal) and 318 mg (1.0 mmol) of thephosphorane VI, (α-formyl-ethylidene)-triphenyl-phosphorane, aredissolved in 5 ml of benzene. The solution is boiled at reflux for 40hours, the benzene is thereupon removed by vacuum, the residue istreated with pentane, the phosphine oxide precipitates this way and isfiltered off and the pentane is again evaporated from the filtrate. Theresidual oil is distilled. There are thus obtained 161 mg (75%) ofgas-chromatographically pure trans β-sinensal VIIa-1(2,6-dimethyl-10-methylene-2t,6t,11-dodecatrienal) of the approximateboiling point 100° /0.1 mm; n_(D) ²⁰ = 1.0577; IR-bands at 1700 s, 1600w, 900 s cm⁻ ¹.

In a corresponding manner, there are obtained by reaction of 158 mg(0.89 mmol) of the cis triene aldehyde Vb-1 with 290 mg (0.91 mmol) ofthe phosphorane VI 157 mg (81%) of cis β-sinensal VIIb-1 of theapproximate boiling point 100° /0.1 mm; n_(D) ²⁰ = 1.5078; IR-bands at1700 s, 1600 w, 900 s cm⁻ ¹.

The phosphorane VI (melting point 220°-222°) can be obtained as follows:Ethyl iodide is reacted in benzene with triphenyl-phosphine to giveethyl-triphenyl-phosphonium iodide, and this is brought to reaction withbutyl-lithium and formic acid methyl ester.

EXAMPLE 5

110 ml of ozone are led into a solution of 15 g (110 mmol) of myrcene in150 ml of ethanol (or methanol) cooled to -80° in the course of about 4hours. The solution is then briefly flushed with nitrogen, in order toexpel excess ozone. A solution of 2.1 g (55.5 mmol) of sodiumborohydride in 100 ml of methanol/water (1:1) is thereupon rapidly addeddropwise at 0° and the mixture is then allowed to react at roomtemperature for 1-2hours. The solution is thereupon concentrated toone-third of the volume at the rotary evaporator (bath-temperature40-50°), the residue taken up in ether, the ether solution thoroughlyshaken twice with 1-molar acetic acid, washed neutral, dried over sodiumsulphate and the ether evaporated off. After fractional distillation,there are obtained 5.8 g (48%) of gas-chromatographically pure4-methylene-5-hexen-1-ol of boiling point 73°-75° /11 mm, n_(D) ²⁰ =1.4790; IR-bands at 3350 s, 1605 m, 900 s cm⁻ ¹.

EXAMPLE 6

10 g (89 mmol) of 4-methylene-5-hexan-1-ol and 22 g (116 mmol) of tosylchloride are dissolved in 50 ml of pyridine. The mixture is allowed toreact at 50° for 1 hour. The reaction product is poured onto a mixtureof ice and 80 ml of concentrated hydrochloric acid and the resultingmixture extracted with ether. The ether extracts are again thoroughlyshaken once each with 1-N hyrochloric acid and with 1-N soda solution.After having been washed neutral with water, the ether solution is driedover sodium sulphate. After evaporation of the ether (bath-temperature40°-50°, ca. 300 mg Hg), there remain approximately 12 g of a crudemixture of the corresponding diene tosylate and diene chloride(6-chloro-3-methylene-1-hexene). The chloride may be purified bydistillation (boiling point 46° /1 mm; n_(D) ²⁰ = 1.4771), but thetosylate is thereby decomposed. For this reason, the tosylate-chloridemixture is converted as such into the iodide.

The tosylate-chloride mixture is dissolved in a suspension of 250 ml ofacetone and 80 g (534 mmol) of sodium iodide and boiled at refluxtemperature with stirring for 16 hours. Ca 200 ml of acetone arethereafter distilled off. The residue is taken up in water/ether. Theether extracts are thoroughly shaken, once with sodium thiosulphatesolution and once with water. After having been dried over sodiumsulphate, the ether is evaporated off. Fractional distillation yields 2fractions:

1. Boiling point 50°-68° /11 mm; 4.1 g; n_(D) ²⁰ = 1.4786 (mainlychloride)

2. Boiling point 68°-76° /11 mm; 4.0 g; n_(D) ²⁰ = 1.5321 (iodide withtrace of chloride)

6 g (27 mmol) of 6-iodo-3-methylene-1-hexene and 14 g (53 mmol) oftriphenyl-phosphine are dissolved in 10 ml of benzene. The mixture isallowed to react at 60° for 24 hours. The(4-methylene-5-hexenyl)-triphenyl-phosphonium iodide which crystallizesout after this time is filtered off by suction, washed with benzene anddried. Yield 10.9 g (84%); melting point 146°.

The 6-Iodo-3-methylene-1-hexene can also be obtained from4methylene-5-hexen-1-ol as follows:

2.02 g (4.5 mmol) of methyl-triphenyloxyphosphonium iodide are dissolvedin 3 ml of absolute methylene chloride and treated at 0° with 0.5 g (4.5mmol) 4-methylene-5-hexen-1-ol (dissolved in 0.6 ml of methylenechloride). After 10 minutes, the mixture is heated and then boiled atreflux temperature for 3 hours. There are thus obtained 333 mg ofgas-chromatographically pure 6-iodo-3-methylene-1-hexene with n_(D) ²⁰ =1.5478; IR-bands at 1600 m, 900 s cm⁻ ¹.

EXAMPLE 7

11.4 g (2.3 mmol) of (4-methylene-5-hexenyl)-triphenylphosphonium iodideare suspended in 80 ml of absolute tetrahydrofuran and 20 ml of absoluteether. 19.4 ml of 1.2-N butyllithium solution (= 2.5 mmol ofbutyl-lithium) in hexane are added to the suspension at -20°. Thesolution thereby turns red. After 30 minutes the solution is cooled to-60° and treated with 4.5 g (2.6 mmol) of 4-oxo-pentanal diethyl acetal(IX: R¹ = C₂ H₅), whereby the red solution decolourises. The mixture issubsequently stirred at room temperature for a further 3.5 hours, thenpoured onto ice-water and extracted with hexane. After drying oversodium sulphate, the hexane is evaporated off. The residual oil ischromatographed on the 10-fold amount of aluminium oxide. Throughelution with benzene, there are obtained 2.6 g of thin layerchromatographically uniform material and therefrom, after distillation,2.4 g (40%) of an oil of boiling point 90° 10.1 mm. On the basis of agas-chromatographic analysis, this product is a cis/trans isomer mixture(2:1) of the triene acetal IV-1 (R¹ = C₂ H₅). IR-bands at 1600 m, 900 scm⁻ ¹.

EXAMPLE 8

2.0 g (8.0 mmol) of cis/trans trieneacetal IV-1 (R¹ =C₂ H₅) aredissolved in 25 ml of dioxan and 8 ml of 0.1-N sulphuric acid. Thesolution is allowed to stand at room temperature for 3 hours. It isneutralised by addition of solid sodium bicarbonate and the product isextracted with ether. After drying the ether extract over sodiumsulphate, evaporation of the solvent and distillation of the residue,there are obtained 1.1 g (77%) of cis/trans triene aldehyde V-1 ofboiling point 100°/0.1 mm; n_(D) ²⁰ = 1.4831; IR-bands at 1730 s, 1600m, 900 s cm⁻ ¹.

EXAMPLE 9

4 g (8.3 mmol) of finely powdered and well dried(4-methylene-5-hexenyl)-triphenyl-phosphonium tetrahydrofuran aresuspended in 24 ml of absolute tetrahydofuran and 8 ml of absolute etherand treated at -20° with 6.8 ml of 1.2-M (8.2 mmol) butyl-lithiumsolution in hexane, whereby the characteristic red colouration rapidlyappears. After having reacted for 30 minutes at -20°, the solution iscooled to -70° and then treated with 1.52 g (8.3 mmol) of6-oxo-2-methyl-2-heptenoic acid ethyl ester X-1 (R² =C₂ H₅). Very rapiddecolourisation of the solution is thereby effected. The mixture isallowed to reach room temperature and stirred for a further 2.5 hours,then poured onto ice/water and extracted with ether. After drying oversodium sulphate, the solvent is evaporated off. There remain 3.7 g of acrude oil which, for the purpose of purification, is subjected tochromatography on the four-fold amount of silica gel (Merck 0.2-0.5).1.3 g of the ester XI (thin layer-chromatographically pure) (R² =C₂ H₅),namely 2,6-dimethyl-10-methylene-2,6,11-dodecatrienoic acid ethyl ester,are eluted with benzene. By a distillation of this product there areobtained 895 mg (41%) of this ester with n_(D) ²⁰ = 1.4938. On the basisof gas-chromatographic analysis, this is an approximately 1:1 mixture ofthe 6-cis and the 6-trans isomers(2,6-dimethyl-10-methylene-2t,6c,11-dodecatrienoic acid ethyl ester and2,6-dimethyl-10-methylene-2t,6t,11-dedecatrienoic acid ethyl ester).

IR-bands at 1705 s, 1650 w, 1600 w, 900 s cm⁻ ¹.

The cis/trans isomer mixture can be separated gas-chromatographically.Cis isomer: n_(D) ²⁰ = 1.4942; trans isomer: n_(D) ²⁰ = 1.4946.

EXAMPLE 10

33 mg (0.25 mmol) anhydrous aluminium chloride and 31 mg (0.78 mmol) oflithium aluminium hydride are suspended in 1 ml of absolute ether. Tothis suspension there are added at -80°, with the exclusion of moisture,90 mg (0.34 mmol) of the cis/trans ester XI-1 obtained in accordancewith Example 9 in a little ether. The reaction mixture is stirred at-30° for 15 minutes, subsequently again cooled to -80° and then treatedwith about 0.5 ml of methanol. The mixture is poured onto ice/0.1-Nhydrochloric acid and extracted with ether. The ether solution is washedneutral with water and dried over sodium sulphate. The oil remainingafter evaporation of the ether is distilled. There are thus obtained 58mg (76%) of the colourless, gas-chromatographically pure cis/transalcohol XII-1 (2,6-dimethyl-10-methylene-2t,6c/t,11-dodecatrienol).IR-bands at 3300 s, 1600 m, 900 s cm⁻ ¹. Boiling point approximately100°/0.1 mm.

EXAMPLE 11

40 mg (0.18 mmol) of the cis/trans alcohol XII-1 obtained in accordancewith Example 10 are added to a suspension of 140 mg of manganese dioxidein 1 ml of hexane. The mixture is stirred in a nitrogen atmosphere atroom temperature for 21 hours, subsequently filtered and the filtratefreed from hexane. By distillation of the residue, there are obtained 19mg (48%) of colourless, gas-chromatographically pure cis/trans aldehydeVII-1 (2,6-dimethyl-10 -methylene-2t,6c/t,11dodecatrienal) of boilingpoint approximately 100° /0.1 mm; IR-bands at 1695 s, 1650 m, 1600 m,900 s cm⁻ ¹.

EXAMPLE 12

1 g (5.6 mmol) of trans triene aldehyde Va-1(4-methyl-8-methylene-4t,9-decadienal) are added to a suspension,previously cooled to -20°, of 3.3 g (9.1 mmol) of(α-carbethoxyethylidene)-triphenyl phosphorane in 12 ml of absolutemethylene chloride, whereupon the reaction mixture is allowed to standfor 30 hours at -20°. After removal of the solvent through vacuum,hexane is added, the precipitated phosphine oxide is filtered off andthe filtrate is concentrated. The residue is distilled in a bulb tube.There are thus obtained 1.25 g (77%) of tetraene ester XI-1(2,6-dimethyl-10-methylen-2t,6t, 11dodecatrienoic acid ethyl ester) inthe form of a colourles oil of b.p. 100°/0.1 mm; IR-bands at 1720 s,1650 w, 1600 w, 900 s cm⁻ ¹.

EXAMPLE 13

37 mmol of ozone are passed in the course of 80 minutes through asolution, previously cooled to -80°, of 5 g (37 mmol) of ocimene in 50ml of methanol. The reaction mixture is thereafter briefly flushed withnitrogen. A solution of 700 mg (19 mmol) of sodium borohydride in 20 mlof methanol/water is then added dropwise at 0°. The mixture is allowedto react at room temperature for 2 hours. The mixture is thenconcentrated to ca one/third of the volume at the rotary evaporator(bath 35°-40° /20 mm Hg). The residue is taken up in ether, thoroughlyshaken with 1-N acetic acid and then again washed neutral with sodiumbicarbonate solution. After drying the organic phase over sodiumsulphate and evaporation of the ether, there remain 3.7 g of crudematerial which, after fractional distillation, yield 1.4 g (34%) of4-methyl-3,5-hexadien-1-ol of boiling point 80°-81°/11 mm, n_(D) ²⁰ =1.4931. IR-bands at 3300 s, 1650 w, 1610 w, 900 s cm⁻ ¹.

The cis/trans isomer mixture of 4-methyl-3,5-hexadien-1-ol may beresolved, e.g. by means of gas chromatography, into the pure cis and thepure trans isomer.

EXAMPLE 14

2.4 g (5.36 mmol) of triphenyl-phosphite-metho-iodide are dissolved in4.5 ml of methylene chloride and treated with 300 mg (2.68 mmol) of4-methyl-3,5-hexadien-1-ol (cis/trans isomere mixture). The reactionmixture is refluxed for 15 minutes in a nitrogen atmosphere. It issubsequently diluted with ether, the ether layer washed three times withice-cold 0.1N soda lye than twice with water and then dried over sodiumsulfate. After removal of the solvent by vacuum an oil remains, which ispurified by chromatography on 10 g of Silicagel (Merck 0.5-0.02). Afterelution of the column with hexane, there are obtained 480 mg (60%) ofpure 6-iode-3-methyl1,3-hexadiene of b.p. 90°/11 mm, n_(D) ²⁰ = 1.5656;IR-bands at 1650 m, 1610 m, 900 s cm⁻ ¹.

In an analogous manner, the pure cis and trans iodide can be obtainedstarting from the corresponding pure cis or trans isomer respectively.

The 6-iodo-3-methyl-1,3-hexadiene obtained is converted in analogy tothe method described in Example 6 with triphenyl phosphine to the(4-methyl-3,5-hexadienyl)-triphenyl phosphonium iodide. Thereby thephosphonium salt of a) the cis/trans isomer mixture of m.p. 113°-120°;b) the trans isomer of m.p. 126°-135°; c) the cis isomer of m.p.102°-110°, are obtained with a yield of about 90%.

EXAMPLE 15

The phosphonium iodide obtained(4-methyl-3,5-hexadienyl)-triphenyl-phosphonium iodide) is condensed ina Wittig reaction with 4-oxo-pentanal diethyl acetal (IX:R¹ ^(-=C) ₂ H₅)to the corresponding triene acetal (4,8-dimethyl-4,7,9-decatrienaldiethylacetal). The reaction is carried out in an analogous manner tothe Wittig reaction described in Example 7. Starting from pure cis andfrom pure trans phosphonium iodide, there is obtained, respectively, anapproximately 7:3 mixture of Δ⁴ -cis/trans, Δ⁷ -cis and of Δ⁴-cis/trans, Δ⁷ -trans triene acetal. B.p. in the bulb tube about100°/0.1 mm; IR -bands at 1650 m, 1600 m, 895 s cm⁻ ¹. The isomers maybe resolved by gas chromatography.

EXAMPLE 16

The obtained triene acetal is saponified to the corresponding trienealdehyde (4,8-dimethyl-4,7,9-decatrienal) in analogy to the process ofExample 8. B.p. in the bulb tube about 90°/0.1 mm; IR-bands at 270 m,1740 s, 1650 m, 1600 m, 900 m cm⁻ ¹.

EXAMPLE 17

In analogy to the process described in Example 12, by a Wittigcondensation of trans/trans triene aldehyde(4,8-dimethyl-4t,7t,9-decatrienal) with(α-carbethoxyethylidene)-triphenyl phosphoran (XIII; R² = C₂ H₅) thecorresponding all-trans tetraene ester(2,6,10-trimethyl-2t,6t,9t,11-dodecatetraenoic acid ethyl ester) isobtained. B.p. in the bulb tube about 100°/0.1 mm; IR-bands at 1715 s,1650 w, 1610 w, 896 m cm⁻ ¹.

EXAMPLE 18

By reduction of the obtained all-trans tetraene ester(2,6,10-trimethyl-2t, 6t, 9t, 11-dodecatetraenoic acid ethyl ester) inanalogy to the process described in Example 10, there is obtained thecorresponding all-trans tetraene alcohol (2,6,10-trimethyl-2t, 6t, 9t,11-dodecatetraenol). B.p. in the bulb tube about 100°-110°/0,1 mm;IR-bands at 3350 s, 1650 m, 1610 m, 995 m, 895 m cm⁻ ¹.

EXAMPLE 19

By oxidation of the obtained all-trans tetraene alcohol(2,6,10-trimethyl-2t, 6t, 9t, 11-dodecatrienol) in analogy to theprocess described in Example 11, there is obtained the correspondingall-trans tetraene aldehyde, αsinensal (2,6,10-trimethyl-2t, 6t, 9t,11-dodecatrienal). B.p. in the bulb tube about 100°/0.1 0.1 mm; IR-bandsat 1725 w, 1650 m, 1610 m, 995 m, 895 m cm⁻ ¹.

EXAMPLE 20

1,6 g of 4-methylene-5-hexen-1-al (see Example 1) are dissolved,together with 5,5 g of silver nitrate, in 14 ml of ethyl alcohol and 7ml of water. 49 ml of 1 n sodium hydroxide are added to the solution andthe mixture is shaken for 20 hours at room temperature. The silver andthe silver oxide are filtered off and the filtrate is extracted withpentane. 240 mg of the starting aldehyde are recovered. The aqueousphase is acidified with hydrochloric acid and extracted thrice withether. The etherextract is washed until neutral, dried and the solventevaporated. Through a subsequent distillation in a bulb tube there areobtained 900 mg of a colorless oil; (50% of the theory); b.p. (bulbtube) of the 4-methylene-5-hexaenoic acid 90°10,1 mm, n_(D) ²⁴,5 1,4752.IR-bands at 1715 s, 1600 m, 910 m.

Esterification of this product with diazomethane yields thecorresponding methylester; b.p. (bulb tube) 85°/11 mm, n_(D) ²⁴²⁰1,4605. IR bands at 3000 s, 1740 s, 1640 w, 1600 m, 1440 s, 900 s.

The foregoing illustrates the practice of this invention, which,however, is not to be limited thereby but is to be construed as broadlyas permissible in view of the prior art and limited solely by theappended claims.

What is claimed is:
 1. A compound having the formula selected from thegroup consisting of ##EQU8## wherein the symbols R¹ each signify a loweralkyl group or together signify a lower alkylene group.
 2. Compounds inaccordance with claim 1 having the formula ##EQU9##
 3. A compound inaccordance with claim 1 having the formula ##EQU10##